LymphomaPhase 3NCT00078949

Chemotherapy Before Autologous Stem Cell Transplantation +/- Rituximab in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

A Phase 3 study testing rituximab, cisplatin and cytarabine in people with Lymphoma, run by NCIC Clinical Trials Group at 27 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 16 to 65 years
Conditions the study is for: Lymphoma
What is being tested?: rituximab, cisplatin and cytarabine
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 849 participants
Where: 27 sitesin 3 countries
Study dates: 27 Aug 2003to Dec 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 to 65 years
All sexes
No healthy volunteers
Child, Adult, Older adult

DISEASE CHARACTERISTICS:

Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following subtypes:
Diffuse large cell lymphoma (includes primary mediastinal B-cell lymphoma and T-cell-rich B-cell lymphoma)
Prior indolent lymphoma (e.g., follicular center cell lymphoma; marginal zone lymphoma, including extranodal mucosa-associated lymphoid tissue [MALT] lymphoma; and lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at relapse
Must be histologically confirmed
No transformed lymphoma at diagnosis with subsequent indolent histology without transformation at relapse
Peripheral T-cell lymphoma
Anaplastic large cell lymphoma
Small noncleaved Burkitt-like lymphoma
T-cell or B-cell lineage confirmed by immunohistochemistry
Clinically or radiologically documented disease meeting either of the following criteria:
Measurable disease, defined as at least 1 bidimensionally measurable site of disease using clinical exam, CT scan, or MRI
Lymph nodes must be > 1.5 cm by physical exam or CT scan
Other non-nodal lesions must be ≥ 1.0 cm by physical exam, CT scan, or MRI
Bone lesions are not considered measurable
Evaluable disease, defined as only nonmeasurable disease, including any of the following:
Marrow infiltration
Cytology-confirmed ascites or effusions
Bony involvement
Enlarged liver or spleen
Unidimensionally measurable intrathoracic or abdominal masses
Previously treated with 1, and only 1, chemotherapy regimen including an anthracycline and excluding cisplatin, cytarabine, and gemcitabine
No uncontrolled CNS involvement by lymphoma
No CNS disease at time of relapse
CNS disease diagnosed at initial presentation allowed provided a complete response for CNS disease was achieved and maintained

PATIENT CHARACTERISTICS:

Age

16 to 65

Performance status

ECOG 0-3

Life expectancy

At least 12 weeks

Hematopoietic

Absolute granulocyte count ≥ 1,000/mm^3
Platelet count ≥ 75,000/mm^3

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST or ALT ≤ 2.5 times ULN (5 times ULN if liver involvement with lymphoma)
Hepatitis B status known (for patients with a history of hepatitis B or who are at high risk of hepatitis B infection)

Renal

Creatinine ≤ 1.5 times ULN

Cardiovascular

No significant cardiac dysfunction or cardiovascular disease

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Willing to complete quality of life questionnaires
HIV negative
No active, uncontrolled bacterial, fungal, or viral infection
No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
No other concurrent serious illness or medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Chemotherapy
Prior rituximab allowed

Chemotherapy

See Disease Characteristics
At least 4 weeks since prior IV chemotherapy
No prior high-dose chemotherapy with stem cell transplantation

Endocrine therapy

No concurrent corticosteroids except for physiologic replacement

Radiotherapy

At least 4 weeks since prior radiotherapy and recovered
Exceptions may be made for low-dose, non-myelosuppressive radiotherapy
No prior radiotherapy to more than 25% of functioning bone marrow
Involved-field radiotherapy may be given to areas of bulky disease at relapse (≥ 5 cm) after stem cell transplantation, according to the center's policy

Surgery

At least 2 weeks since prior major surgery

Other

No other concurrent anticancer therapy
No other concurrent experimental agents

Trial locations and contacts

27 sites in 3 countries.

Country

City, postcode or hospital

27 sites in 3 countries

Canada21 sites

Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Hopital Charles LeMoyne
Greenfield Park, Quebec, J4V 2H1
QEII Health Sciences Center
Halifax, Nova Scotia, B3H 1V7
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, L8V 5C2
Cancer Centre of Southeastern Ontario at Kingston
Kingston, Ontario, K7L 5P9
London Regional Cancer Program
London, Ontario, N6A 4L6
Credit Valley Hospital
Mississauga, Ontario, L5M 2N1
The Moncton Hospital
Moncton, New Brunswick, E1C 6Z8
CHUM - Hopital Notre-Dame
Montreal, Quebec, H2L 4M1
CHUQ-Pavillon Hotel-Dieu de Quebec
Québec, Quebec, G1R 2J6
CHA-Hopital Du St-Sacrement
Québec, Quebec, G1S 4L8
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Centre hospitalier universitaire de Sherbrooke
Sherbrooke, Quebec, J1H 5N4
Dr. H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, AIB 3V6
Thunder Bay Regional Health Science Centre
Thunder Bay, Ontario, P7B 6V4
Odette Cancer Centre
Toronto, Ontario, M4N 3M5
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

United States5 sites

Rush-Presbyterian-St. Luke's Medical Centre
Chicago, Illinois, 60612
University of Cincinnati, Barrett Cancer Centre
Cincinnati, Ohio, 45219
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Indiana University Medical Center
Indianapolis, Indiana, 46202
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232

Other trials in United States

Australia1 site

The Queen Elizabeth Hospital
Woodville, South Australia, 5011

Other trials in Australia

About this study

Official title: Phase III Study Of Gemcitabine, Dexamethasone, And Cisplatin Compared To Dexamethasone, Cytarabine, And Cisplatin Plus/Minus Rituximab [(R)-GDP vs (R)-DHAP] As Salvage Chemotherapy For Patients With Relapsed Or Refractory Aggressive Histology Non-Hodgkin's Lymphoma Prior To Autologous Stem Cell Transplant And Followed By Maintenance Rituximab vs Observation

RATIONALE: Drugs used in chemotherapy, such as dexamethasone, cisplatin, gemcitabine, and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving rituximab as maintenance therapy after stem cell transplantation may kill any remaining cancer cells. It is not yet known which salvage chemotherapy regimen is more effective before autologous stem cell transplantation in treating relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying salvage chemotherapy using dexamethasone, cisplatin, and gemcitabine to see how well it works compared to dexamethasone, cisplatin, and cytarabine given before autologous stem cell transplantation in treating patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. This trial also is studying giving rituximab as maintenance therapy to see how well it works compared to no further therapy after stem cell transplantation. Rituximab was added to both salvage treatment arms for CD20+ patients in a protocol amendment in 2005.

Read the detailed description

OBJECTIVES:

Salvage therapy

Primary

Compare the response rate and transplantation rate in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma when treated with salvage chemotherapy comprising dexamethasone, cisplatin, and gemcitabine with or without rituximab vs a standard platinum-based regimen (dexamethasone, cisplatin, and high-dose cytarabine with or without rituximab).
To compare the transplantation rates of the two protocol salvage regimens.

Secondary

Compare the event-free and overall survival of patients treated with these regimens.
Compare the success rate of these regimens, in terms of getting patients to autologous stem cell transplantation and successful mobilization after high-dose chemotherapy.
Compare the quality of life of patients treated with these salvage regimens.
Compare the toxic effects of these salvage regimens in these patients.
Compare resource utilization for patients treated with these salvage regimens.
Compare relative medical and societal costs of these salvage regimens with outcomes in these patients.

Maintenance therapy

Primary

Compare the 2-year event-free survival of patients with CD20+ B-cell lymphoma treated with maintenance rituximab after these salvage regimens and autologous stem cell transplantation to those patients who received no further treatment.

Secondary

Compare the 2-year survival of patients treated with or without maintenance rituximab.
Compare the toxic effects of rituximab vs observation alone in these patients.

OUTLINE: This is a randomized, multicenter study. For salvage therapy, patients are stratified according to participating center, International Prognostic Index score at relapse/study entry (0 or 1 vs 2 vs ≥ 3), immunophenotype (B cell vs T cell), response to or response duration after initial chemotherapy (no response or progressive disease vs > 1 year vs ≤ 1 year), and prior rituximab (yes vs no). For maintenance therapy, patients are stratified according to participating center, salvage therapy treatment randomization (with or without rituximab, cisplatin, dexamethasone, and gemcitabine vs with or without rituximab, cisplatin, dexamethasone, and cytarabine), response to salvage therapy (complete response [CR] and CR unconfirmed [CRu] vs partial response [PR] vs stable disease [SD]), and prior rituximab (yes vs no).

Salvage therapy: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1.
Arm II: Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1.

In both arms, treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are reassessed after 2 courses. Patients with progressive disease are removed from study. Patients with a CR, CRu, or PR proceed to autologous stem cell transplantation (ASCT). Patients with SD may proceed to ASCT or receive 1 additional course of salvage therapy at the discretion of the investigator. Patients receiving an additional course of salvage therapy are then reassessed after the completion of therapy. Patients with progressive disease are removed from study. Patients with a PR proceed to ASCT. Patients with SD may proceed to ASCT or be followed off study at the discretion of the investigator.

ASCT: Responding patients (or those with stable disease, if that is the center's policy)undergo mobilization, stem cell harvest, and subsequent ASCT. Patients with CD20+ B-cell disease are randomized to maintenance therapy or observation.
Maintenance therapy: Patients are randomized to 1 of 2 treatment arms.
Arm I: Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity.
Arm II: Patients undergo observation only. Quality of life is assessed at baseline, days 1 and 10 of course 2, day 1 of course 3 (if given), on the last day of salvage therapy (or the first day of mobilization, if given), and at 1 month posttransplantation.

Patients who undergo ASCT are followed at months 1, 3, 7, 13, 19, and 25 and then annually thereafter. Patients who complete salvage therapy, but do not undergo ASCT are followed at months 4, 8, 14, 20, and 26 and then annually thereafter. Patients who relapse or progress are followed every 6 months until 25 months from ASCT or 26 months from completion of salvage therapy and then annually thereafter.

PROJECTED ACCRUAL: A total of 637 patients will be accrued for this study within 3-4 years for the first randomization, and 240 transplanted CD20+ patients will be needed for the second randomization.

Conditions: Lymphoma
Being tested: rituximab, cisplatin, cytarabine, dexamethasone, gemcitabine hydrochloride
Keywords: anaplastic large cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, angioimmunoblastic T-cell lymphoma
Medical subject headings: Lymphoma, Lymphoma, Large-Cell, Anaplastic, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Immunoblastic Lymphadenopathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

rituximabBiological
Given IV
cisplatinDrug
Given IV
cytarabineDrug
Given IV
dexamethasoneDrug
Given IV
gemcitabine hydrochlorideDrug
Given IV

Study groups in NCT00078949
Study group	Role	What they receive
Salvage arm I	Experimental	Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Receives: Drug: cisplatin; Drug: dexamethasone; Drug: gemcitabine hydrochloride
Salvage arm II	Experimental	Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. Receives: Drug: cisplatin; Drug: cytarabine; Drug: dexamethasone
Maintenance arm I	Experimental	Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity. Receives: Biological: rituximab
Maintenance arm II	No intervention	Patients undergo observation only.

What is being measured

The primary outcome is the main question the study is designed to answer.

Response Rate of Patients After 2 Courses of Chemotherapy
The overall response rate by arm is calculated as total number of responders (CR + CRu + PR) / (all patients in the ITT analysis population).
Measured: After 2 cycle of treatment
Transplantation Rate of Patients After 2 Courses of Chemotherapy
Transplantation rate is defined as the number of patients who respond sufficiently to protocol salvage chemotherapy to be planned for transplantation minus those who do not meet the endpoint of successful transplantation, divided by the number of all randomized patients
Measured: During period 1 (salvage chemotherapy)
Event-free Survival of Patients on Maintenance Randomization (Period 2)
Number of patients who develop EFS event during maintenance randomization (period 2)
Measured: during the period 2 (up to10 years)

Secondary outcomes (1)

Toxic Effect
Number of patients affected by adverse events graded according to CTC Version 2.0. See adverse event (others) for details.
Measured: 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Aug 2003Dec 2018

First posted9 Mar 2004 (estimated)
Study start27 Aug 2003
Primary completion29 Jul 2013
Study completionDec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (7)Papers the sponsor has linked to this study.
Other trials for LymphomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 849 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00078949
Sponsor's protocol ID: LY12
Other IDs: CAN-NCIC-LY12, CDR0000353203
Status last verified: Mar 2020
First submitted: 8 Mar 2004
Last updated: 23 Aug 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Gupta A, Hay AE, Crump M, Djurfeldt MS, Zhu L, Cheung MC, Shepherd LE, Chen BE, Booth CM. Contact Days Associated With Cancer Treatments in the CCTG LY.12 Trial. Oncologist. 2023 Sep 7;28(9):799-803. doi: 10.1093/oncolo/oyad128.
PubMed 37226534
Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. doi: 10.1200/JCO.2013.53.9593. Epub 2014 Sep 29.
PubMed 25267740
Gupta A, Thomas T, Hay AE, Crump M, Djurfeldt MS, Cheung MC, Prica A, Shepherd LE, Chen BE, Booth CM. The association of health care contact days with economic measures in the CCTG LY.12 trial. Oncologist. 2025 Jun 4;30(6):oyaf165. doi: 10.1093/oncolo/oyaf165.
PubMed 40503814
Assouline S, Li S, Gisselbrecht C, Fogarty P, Hay A, van den Neste E, Shepherd LE, Schmitz N, Baetz T, Keating A, Robinson S, Seftel M, Stelitano C, Djurfeldt MS, Meyer R, Chen BE, Crump M. The conditional survival analysis of relapsed DLBCL after autologous transplant: a subgroup analysis of LY.12 and CORAL. Blood Adv. 2020 May 12;4(9):2011-2017. doi: 10.1182/bloodadvances.2020001646.
PubMed 32396614
Bosch M, Akhter A, Chen BE, Mansoor A, Lebrun D, Good D, Crump M, Shepherd L, Scott DW, Stewart DA. A bioclinical prognostic model using MYC and BCL2 predicts outcome in relapsed/refractory diffuse large B-cell lymphoma. Haematologica. 2018 Feb;103(2):288-296. doi: 10.3324/haematol.2017.179309. Epub 2017 Nov 2.
PubMed 29097500
Davison K, Chen BE, Kukreti V, Couban S, Benger A, Berinstein NL, Kaizer L, Desjardins P, Mangel J, Zhu L, Djurfeldt MS, Hay AE, Shepherd LE, Crump M. Treatment outcomes for older patients with relapsed/refractory aggressive lymphoma receiving salvage chemotherapy and autologous stem cell transplantation are similar to younger patients: a subgroup analysis from the phase III CCTG LY.12 trial. Ann Oncol. 2017 Mar 1;28(3):622-627. doi: 10.1093/annonc/mdw653.
PubMed 27993811
Kuruvilla J, MacDonald DA, Kouroukis CT, Cheung M, Olney HJ, Turner AR, Anglin P, Seftel M, Ismail WS, Luminari S, Couban S, Baetz T, Meyer RM, Hay AE, Shepherd L, Djurfeldt MS, Alamoudi S, Chen BE, Crump M. Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC CTG LY12. Blood. 2015 Aug 6;126(6):733-8. doi: 10.1182/blood-2015-01-622084. Epub 2015 Jun 24.
PubMed 26109202

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Lymphoma trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase III Study Of Gemcitabine, Dexamethasone, And Cisplatin Compared To Dexamethasone, Cytarabine, And Cisplatin Plus/Minus Rituximab [(R)-GDP vs (R)-DHAP] As Salvage Chemotherapy For Patients With Relapsed Or Refractory Aggressive Histology Non-Hodgkin's Lymphoma Prior To Autologous Stem Cell Transplant And Followed By Maintenance Rituximab vs Observation
ClinicalTrials.gov ID: NCT00078949
Acronym / sponsor ID: LY12
Conditions: Lymphoma
Keywords: anaplastic large cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, angioimmunoblastic T-cell lymphoma
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 849 participants (actual)
Lead sponsor: NCIC Clinical Trials GroupResearch network
Study start: 27 Aug 2003 (actual)
Primary completion: 29 Jul 2013 (actual)
Study completion: Dec 2018 (actual)
First posted: 9 Mar 2004 (estimated)
Results: Posted 21 Oct 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

OBJECTIVES:

Salvage therapy

Primary

Compare the response rate and transplantation rate in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma when treated with salvage chemotherapy comprising dexamethasone, cisplatin, and gemcitabine with or without rituximab vs a standard platinum-based regimen (dexamethasone, cisplatin, and high-dose cytarabine with or without rituximab).
To compare the transplantation rates of the two protocol salvage regimens.

Secondary

Compare the event-free and overall survival of patients treated with these regimens.
Compare the success rate of these regimens, in terms of getting patients to autologous stem cell transplantation and successful mobilization after high-dose chemotherapy.
Compare the quality of life of patients treated with these salvage regimens.
Compare the toxic effects of these salvage regimens in these patients.
Compare resource utilization for patients treated with these salvage regimens.
Compare relative medical and societal costs of these salvage regimens with outcomes in these patients.

Maintenance therapy

Primary

Compare the 2-year event-free survival of patients with CD20+ B-cell lymphoma treated with maintenance rituximab after these salvage regimens and autologous stem cell transplantation to those patients who received no further treatment.

Secondary

Compare the 2-year survival of patients treated with or without maintenance rituximab.
Compare the toxic effects of rituximab vs observation alone in these patients.

Salvage therapy: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1.
Arm II: Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1.

In both arms, treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

ASCT: Responding patients (or those with stable disease, if that is the center's policy)undergo mobilization, stem cell harvest, and subsequent ASCT. Patients with CD20+ B-cell disease are randomized to maintenance therapy or observation.
Maintenance therapy: Patients are randomized to 1 of 2 treatment arms.
Arm I: Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity.
Arm II: Patients undergo observation only. Quality of life is assessed at baseline, days 1 and 10 of course 2, day 1 of course 3 (if given), on the last day of salvage therapy (or the first day of mobilization, if given), and at 1 month posttransplantation.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Salvage arm I	Experimental	Drug: cisplatin, Drug: dexamethasone, Drug: gemcitabine hydrochloridePatients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8.
Salvage arm II	Experimental	Drug: cisplatin, Drug: cytarabine, Drug: dexamethasonePatients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2.
Maintenance arm I	Experimental	Biological: rituximabBeginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity.
Maintenance arm II	No intervention	–Patients undergo observation only.

Who may qualify

Ages: 16 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
rituximabGiven IV	Biological	Maintenance arm I
cisplatinGiven IV	Drug	Salvage arm I, Salvage arm II
cytarabineGiven IV	Drug	Salvage arm II
dexamethasoneGiven IV	Drug	Salvage arm I, Salvage arm II
gemcitabine hydrochlorideGiven IV	Drug	Salvage arm I

Primary outcome

Response Rate of Patients After 2 Courses of Chemotherapy
Time frame: After 2 cycle of treatment
The overall response rate by arm is calculated as total number of responders (CR + CRu + PR) / (all patients in the ITT analysis population).
Transplantation Rate of Patients After 2 Courses of Chemotherapy
Time frame: During period 1 (salvage chemotherapy)
Transplantation rate is defined as the number of patients who respond sufficiently to protocol salvage chemotherapy to be planned for transplantation minus those who do not meet the endpoint of successful transplantation, divided by the number of all randomized patients
Event-free Survival of Patients on Maintenance Randomization (Period 2)
Time frame: during the period 2 (up to10 years)
Number of patients who develop EFS event during maintenance randomization (period 2)

1 secondary outcome

Toxic Effect
Time frame: 48 months

Results and safety

Results posted to the registry on 21 Oct 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Salvage GDP	310	306
Salvage DHAP	309	304
Maintenance	115	112
Observation	115	112

Primary outcome: Response Rate of Patients After 2 Courses of Chemotherapy

Time frame: After 2 cycle of treatment. Number. Unit: percentage of response

Measure	Salvage GDP n = 310	Salvage DHAP n = 309
Value	45.2	44.0

Salvage GDP vs Salvage DHAP: Risk Difference (RD): -1.2 (95% CI -9.0 to 6.7), p = 0.005, Cochran-Mantel-Haenszel

Population analysed: ITT population

Primary outcome: Transplantation Rate of Patients After 2 Courses of Chemotherapy

Time frame: During period 1 (salvage chemotherapy). Number. Unit: percentage of transplantation

Measure	Salvage GDP n = 310	Salvage DHAP n = 309
Value	51.0	48.9

Salvage GDP vs Salvage DHAP: Risk Difference (RD): -2.1 (95% CI -10.0 to 5.8), p = 0.55, Cochran-Mantel-Haenszel

Primary outcome: Event-free Survival of Patients on Maintenance Randomization (Period 2)

Time frame: during the period 2 (up to10 years). Number. Unit: participants

Measure	Maintenance n = 115	Observation n = 115
Value	53	65

Maintenance vs Observation: Hazard Ratio (HR): 0.77 (95% CI 0.52 to 1.12), p = 0.17, Log Rank

Population analysed: ITT population

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 8.5 year. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Salvage GDP	36 of 306 (11.8%)	287 of 306 (93.8%)	177 of 310
Salvage DHAP	26 of 304 (8.6%)	293 of 304 (96.4%)	181 of 309
Maintenance	16 of 112 (14.3%)	98 of 112 (87.5%)	39 of 115
Observation	8 of 112 (7.1%)	90 of 112 (80.4%)	42 of 115

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 37226534Gupta A, Hay AE, Crump M, Djurfeldt MS, Zhu L, Cheung MC, Shepherd LE, Chen BE, Booth CM. Contact Days Associated With Cancer Treatments in the CCTG LY.12 Trial. Oncologist. 2023 Sep 7;28(9):799-803. doi: 10.1093/oncolo/oyad128.
Results publication: PubMed 25267740Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. doi: 10.1200/JCO.2013.53.9593. Epub 2014 Sep 29.
Derived from this study: PubMed 40503814Gupta A, Thomas T, Hay AE, Crump M, Djurfeldt MS, Cheung MC, Prica A, Shepherd LE, Chen BE, Booth CM. The association of health care contact days with economic measures in the CCTG LY.12 trial. Oncologist. 2025 Jun 4;30(6):oyaf165. doi: 10.1093/oncolo/oyaf165.
Derived from this study: PubMed 32396614Assouline S, Li S, Gisselbrecht C, Fogarty P, Hay A, van den Neste E, Shepherd LE, Schmitz N, Baetz T, Keating A, Robinson S, Seftel M, Stelitano C, Djurfeldt MS, Meyer R, Chen BE, Crump M. The conditional survival analysis of relapsed DLBCL after autologous transplant: a subgroup analysis of LY.12 and CORAL. Blood Adv. 2020 May 12;4(9):2011-2017. doi: 10.1182/bloodadvances.2020001646.
Derived from this study: PubMed 29097500Bosch M, Akhter A, Chen BE, Mansoor A, Lebrun D, Good D, Crump M, Shepherd L, Scott DW, Stewart DA. A bioclinical prognostic model using MYC and BCL2 predicts outcome in relapsed/refractory diffuse large B-cell lymphoma. Haematologica. 2018 Feb;103(2):288-296. doi: 10.3324/haematol.2017.179309. Epub 2017 Nov 2.
Derived from this study: PubMed 27993811Davison K, Chen BE, Kukreti V, Couban S, Benger A, Berinstein NL, Kaizer L, Desjardins P, Mangel J, Zhu L, Djurfeldt MS, Hay AE, Shepherd LE, Crump M. Treatment outcomes for older patients with relapsed/refractory aggressive lymphoma receiving salvage chemotherapy and autologous stem cell transplantation are similar to younger patients: a subgroup analysis from the phase III CCTG LY.12 trial. Ann Oncol. 2017 Mar 1;28(3):622-627. doi: 10.1093/annonc/mdw653.
Derived from this study: PubMed 26109202Kuruvilla J, MacDonald DA, Kouroukis CT, Cheung M, Olney HJ, Turner AR, Anglin P, Seftel M, Ismail WS, Luminari S, Couban S, Baetz T, Meyer RM, Hay AE, Shepherd L, Djurfeldt MS, Alamoudi S, Chen BE, Crump M. Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC CTG LY12. Blood. 2015 Aug 6;126(6):733-8. doi: 10.1182/blood-2015-01-622084. Epub 2015 Jun 24.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael R. Crump, MD, FRCPC study chair

Princess Margaret Hospital, Canada

Massimo Federico, MD study chair

Azienda Ospedaliero-Universitaria di Modena

27 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing rituximab, cisplatin and cytarabine in people with Lymphoma, run by NCIC Clinical Trials Group at 27 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Canada, United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response Rate of Patients After 2 Courses of Chemotherapy (time frame: After 2 cycle of treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00078949, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2023.